Animal Models of Parkinson’s Disease

We offer multiple animal models of Parkinson’s disease studies to support your research. All of our animal models of Parkinson’s disease track induction, behavioral deficits, and monoamine levels and can be further investigated with in vivo imaging and neuropathology.

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6-OHDA Rat Study

The 6-OHDA rat model is a chemically induced intrastriatal model that is used to monitor two behavioral deficits: rotational asymmetry and motor defects. The monoamine levels assessed in this model are decreased dopamine and DOPAC and HVA content in the striatum. The in vivo imaging offered is DAT PET, F-DOPA PET, and T2-weighted MRI. You can further analyze your data with our neuropathology services: TH-positive cells in the substantia nigra or Striatal TH (western blot), and microglial activation.

  • Study Paradigm:

    Image showing the timeline for the 6-OHDA Rat model offered at Charles River.

  • Validation Data:

    6-OHDA Model Biomarkers: Dopamine and its metabolites, dopamine transporter, tyrosine hydroxylase

    A graph of dopamine and its metabolites rom Vehicle and 6-OHDA treatment groups.

    Neurochemistry: Total dopamine (DA) and its metabolites DOPAC and HVA along with serotonin (5-HT) concentrations in left (A) and right (B) striatum on D37 after the 6-OHDA injection. Incomplete lesion (R14) highlighted with a red circle.

    Tyrosine hydroxylase (TH): Reduction in TH can be followed with immune histochemistry or Western blot.

    Dopamine transport (DAT): Reduction in dopamine transporter (DAT) density on the 6-OHDA lesioned side in PET imaging.

    6-OHDa Model Immunohistochemistry: TH and iba1 staining in SNc

    Immunohistochemistry of striatum of Vehicle versus 6-OHDA treatment groups and a graph of the quantification of these two groups.

    Decrease in TH positive cells can be visually observed in the sections Estimated TH-positive cell count in substantia nigra on D36 after lesioning (multiple t-test, n = 10 SHAM, n = 15 6-OHDA). Incomplete lesion (R14) highlighted with red a circle.

    A graph of quantification of Iba-1 of immunohistochemistry stained striatum after 6-OHDA lesioning

MPTP Mouse Study

The MPTP Mouse model is a chemically induced model that is used to monitor behavioral defects. The monoamine levels monitored in this model are decreased dopamine, DOPAC, and HVA content in the striatum. The in vivo imaging offered is DAT PET, FDG PET, and MRS. You can further analyze your data with our neuropathology services: TH-positive cells in the substantia nigra.

  • Study Paradigm:

    Image showing the timeline for the MPTP Mouse model offered at Charles River. The MPTP Mouse model is a validated study model that can support your Parkinson’s Disease research.

  • Validation Data:

    Graphs of 18FDG update in the striatum before and after MPTP treatment. There is significantly more uptake before treatment.

    MPTP Mouse Model: PET Imaging

    PET imaging of MPTP and vehicle treated mouse brain.

    PET Imaging:

    • Striatal DAT density is decreased in MPTP-treated mice. PET imaging with DAT ligand 18F-FE-PE2I 4 weeks post MPTP challenge 20 mg/kg i.p.
    • Reduced glucose metabolism in striatum in MPTP-treated mice. PET imaging with 18F-FDG 6 weeks post MPTP challenge 20 mg/kg i.p.
    • p < 0.05, ** p < 0.01, **** p < 0.0001,
    • MPTP 20mg/kg i.p. vs. Control (Welch’s t-test)
    • Data presented as mean + SEM

    MPTP Mouse Model: Neurochemistry

    Grpahs of LC-MS data of dopamine metabolites from MPTP treated mouse brains.

    ***p<0.001, ****p<0.0001 MPTP veh. vs. Saline vehl. ##p<0.01, ###p<0.001. Nilotinib 25mg/kg + MPTP 20mg/kg i.p. (Welch’s t-test). Data are presented as mean + SEM.

    Nilotinib effect: MPTP produces a dramatic reduction in striatal dopamine (DA), DOPAC, and HVA levels, which is rescued by nilotinib, a tyrosine kinase inhibitor.

    MPTP Mouse Model:

    TH staining in SNc
    TH Positive Cells in SNpc Bilaterally

    Graph of tyrosine hydroxylast positive cells before and after MPTP and Nilotinib treated mouse brains in the substantia nigra pars compacta.

    *** p < 0.001 MPTP + Veh vs. Saline Vehicle. ## p < 0.001 MPTP + Veh vs. Nilotinib. No statistical difference between Saline-Veh and MPTP Nilotinib groups. (Welch’s t-test). N=15/group. Data are presented as mean ± SEM.

    Tyrosine hydroxylase (TH) positive cell counts: The number of TH-positive cells in the SNc of MPTP-treated mice is decreased. Nilotinib, a tyrosine kinase inhibitor, partially reverses the effect of MPTP treatment on the number of TH-positive cells.

AAV-A53T-aSyn Animal Studies

The AAV-A53T-aSyn Animal Model is available in both rat and mouse models. It is a biological transduction model that monitors two behavioral deficits: rotational asymmetry (rats) and motor defects (rats and mice). The monoamine levels monitored in this model are decreased dopamine and DOPAC and HVA content in the striatum. The in vivo imaging offered for this model is DAT PET. You can further analyze your data with our neuropathology services: TH-positive cells in the substantia nigra and aSyn immunoreactivity.

  • Study Paradigm:

    Image showing the timeline for the AAV-A53T-aSyn Animal model offered at Charles River. The AAV-A53T-aSyn Animal model is a validated study model that can support your Parkinson’s disease research.

  • Validation Data:

    MPTP Mouse Model: Neuroinflammation

    Iba-1 positive cells in a transgenic mouse model of Parkinson’s disease.

    ** p < 0.01; *** p < 0.001, **** p < 0.0001. AAV control vs. AAV A53T (Welch’s t-test). Data are presented as mean + SEM.

    Microglial Activation: Levels of Iba-1, a marker for microglia, is increased in the SNpc at 5 weeks post infusion. N=15

    AAV-A53T Mouse Model: Biomarkers

    Graph showing the AAV-A53T mouse model

    ** p < 0.01; *** p < 0.001, **** p < 0.0001. AAV control vs. AAV A53T (Welch’s t-test). Data are presented as mean + SEM.

    TH-positive Cells
    In stereological analysis, there is a decreased number of TH-immunopositive cells in the ipsilateral side to the infusion side in AAV α-synuclein animals 9 weeks post infusion.

    Graph showing TH-positive cells

    Upper row: AAV-A53T (1.7 x 1012 vg/mL)

    Lower row: Null-vector (1.7 x 1012 vg/mL)

    Left Panel: Anti-TH staining

    Middle Panel: Anti-asyn staining

    Right Panel: Anti-TH/asyn combined

    α-synuclein Immunoreactivity: Immunoreactivity has been observed only in the ipsilateral substantia nigra of the AAV-A53T-aSyn dosed animals.

 

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Frequently Asked Questions (FAQs) for Animal Models of Parkinson’s Disease